Activated mono,di,oligo- and polysaccharides, reaction products thereof, their preparation and uses

ABSTRACT

Reaction at the interface of an organic solution containing an acidic reactant and an aqueous alkaline solution containing nonreducing carbohydrates such as sucrose, sugar alcohols, cyclodextrins, and polysaccharides imparts a specificity to the reaction for one or more of the primary alcohol groups of the carbohydrate reactant. The resulting activated, nonreducing carbohydrate intermediate can then be converted to a series of substantially pure, low molecular weight reaction products, including a sucrose trimer and dianhydrosucrose, and to a series of substantially pure, higher molecular weight reaction products, including 6-O-sucro cyclodextrins and poly-6-O-sucro amylose.

This application is a division of application Ser. No. 08/880,152 filedJun. 20, 1997, now U.S. Pat. No. 5,900,478.

FIELD OF THE INVENTION

This invention relates to new and useful sucrose derivatives, theparticular methods for their syntheses, and the use of the products.

BACKGROUND OF THE INVENTION

The most abundant pure organic compound in the world is sucrose. SeeKirk-Othmer, Encyclopedia of Chemical Technology, 3rd Edition, Volume21, John Wiley & Sons, New York, pages 921-948 (1983). However, althoughsucrose produced from sugar cane and sugar beets is ubiquitous in itsavailability and is of relatively low cost, only a fraction of a percentby weight is consumed as a chemical feedstock. The potential value ofsucrose as a raw material has been recognized for many years and hasbeen the subject of considerable research.

Sucrose and assorted polyols, including polysaccharides, areparticularly appropriate materials for use in the formation ofesterified and etherified products produced currently frompetroleum-based materials because they (a) are naturally occurring,relatively abundant renewable materials; (b) are polyfunctional withmultiple reactive primary alcohols that can readily be derivatized; (c)are nonreducing carbohydrates and thus do not have the potential for thewide variety of side-reactions characteristic of reducing carbohydrates;(d) have relatively easily hydrolyzed glycosidic linkages that allowpolymers made from such materials to be potentially more biodegradablethan similar polymers made with hydrogenated carbohydrates, such assugar alcohols; and (e) are naturally occurring products in common useand therefore potentially useful in the formation of novel ingredientsfor the food, beverage, pharmaceutical, and chemical industries.

SUMMARY OF THE INVENTION

It is an object of the invention described herein to provide novelmethods for the preparation of substantially pure saccharide derivativeswhich are useful as food bulking agents, food dietary fibers, reducedcalorie sweeteners, fat replacement materials, adhesives, thickening andemulsifying agents for food products, biodegradable plastics and films,sizing agents for paper and textiles, ethical pharmaceuticals, newdentifrices, and new fibers.

A further object of the present invention is the provision of a methodfor preparing polysaccharide derivatives in high yields and withimproved specificity as compared to methods known to the prior art.

An even further object of the invention is to provide a method for thepreparation of activated sucrose, activated sugar alcohols, activatedoligosaccharides, or activated polysaccharides in substantially pureforms which have facile leaving groups at multiple primary hydroxylpositions, thus providing activated reactants which can be used tosynthesize a number of additional new products.

An even further object of the present invention is to provide activatedsucrose, activated sugar alcohol, activated oligosaccharide, oractivated polysaccharide intermediates wherein the activated sucrose,activated sugar alcohol, activated oligosaccharides, or activatedpolysaccharide intermediate can be reacted with another moleculeincluding single or multiple saccharides so as to form a novel series ofhighly useful products.

In satisfaction of the foregoing objects and advantages, the presentinvention provides in one embodiment a method for preparation of anactivated polysaccharide by reaction of the polysaccharide with areactant which will provide a facile leaving group, e.g. tosyl(p-toluenesulfonyl) or trityl (triphenylmethyl), at various primaryhydroxyl groups of the polysaccharide. The reaction is conducted byadding a tosyl or trityl halide contained in a water-immiscible organicsolvent to the polysaccharide contained in an alkaline aqueous solution,and recovering the product.

In a main embodiment, the present invention provides substantially puresulfonyl substituted nonreducing mono-, di-, oligo- and polysaccharides,wherein the monosaccharides are represented by the sugar alcohols suchas xylitol and glucitol, the disaccharides are represented by sucrose,the oligosaccharides are represented by the cyclodextrins, and thepolysaccharides are represented by cellulose, amylose, amylopectin,pullulan, and chitosan and their lower molecular weight analogs.

The present invention also provides activated sucrose intermediateproducts containing facile leaving groups at the 6- and 6'-positions ofsucrose, and methods for conversion of the activated sucroseintermediate products by a condensation reaction with other molecules,e.g., mono-, di-, tri-, oligo- and polysaccharides, to producesubstantially pure condensed sucrose products which are novel and highlyuseful materials.

The present invention further provides activated sugar alcoholintermediate products containing facile leaving groups at the primaryhydroxyl positions of the sugar alcohol, and methods for conversion ofthe activated sugar alcohol intermediates by a condensation reactionwith other molecules, e.g., mono-, di-, tri-, oligo- andpolysaccharides, to produce substantially pure condensed sugar alcoholproducts which are novel and highly useful materials.

Also provided by the present invention are sucrose products substitutedat the 6- and 6'-positions, and sugar alcohol, oligosaccharide, andpolysaccharide products substituted at various primary methylenepositions by substituents such as halogen, amino, carboxylic acidesters, etc., such products being formed by reaction of the activatedsucrose, sugar alcohol, oligosaccharide, or polysaccharide with anappropriate reactant which will effect nucleophilic displacement.

Other objects and advantages of the present invention will becomeapparent as the description thereof proceeds.

DETAILED DESCRIPTION OF THE INVENTION

The present invention involves reactions of certain reagents withpolysaccharides, oligosaccharides, sugar alcohols or sucrose, the latterhaving the following structure and, numbering system for the reactivehydroxyl groups and corresponding carbon atoms: ##STR1##

Through the reactions of this invention it has been discovered that onecan direct the specificity of the reactions to the 6- and 6'-positionsof sucrose, and corresponding equivalent positions within sugaralcohols, oligosaccharides, and polysaccharides, and thus form activatedsucrose, sugar alcohols, oligosaccharides, or polysaccharides which areimportant intermediates in the preparation of a novel and useful seriesof sucrose, sugar alcohol, oligosaccharide, or polysaccharide reactionproducts, and also in the formation of other useful derivatives. Becausethe reactions are very specific, the activated sucrose, sugar alcohol,oligosaccharide, or polysaccharide is substantially pure, and unwantedside products are avoided.

According to the present invention, both low molecular weight productsand high molecular weight products can be produced. Low molecular weightproducts are produced from disaccharides such as sucrose and sugaralcohols such as alditols and pentitols.

Low Molecular Weight Reaction Products

By use of a two-phase reaction system, the processes of the presentinvention in a major embodiment produce "activated sucrose" and"activated sugar alcohols" which have facile sulfonyl leaving groups atthe activated primary hydroxyl positions. Because of the relatively lowcost and ready availability of tosyl chloride, tosyl is the mosteconomical facile leaving group. While tosyl is the preferred leavinggroup, other sulfonyl groups may also be used. While the reaction iseffective with nonreducing carbohydrates in general, the presentinvention is described herein with respect to sucrose and sugar alcoholsas the preferred starting materials.

The present invention provides a procedure by which the 6-, 6'-, and/or1'-positions of sucrose, and one or more of the primary alcohol groupswithin sugar alcohols, can be activated or made reactive in a specificmanner so that a wide series of new sucrose and sugar alcohol productscan be produced. The new sucrose products contain such linkages thatthese new products are useful as food bulking agents providingproperties characteristic of sucrose. The new sucrose reaction productsare also noncaloric and noncariogenic. The new sugar alcohol productscontain linkages that make these new products useful as food andnon-food materials requiring properties characteristic of sugaralcohols.

The present invention provides three significant new types of products,i.e.,

a. activated sucrose and activated sugar alcohols by substitution of oneor more tosyl or trityl groups on the primary alcohols within theactivated sucrose or activated sugar alcohol;

b. reaction of the activated sucrose with sucrose or various sugaralcohols, or reaction of the activated sugar alcohol with sucrose orwith the same or different sugar alcohol, to form sucrose-sucrose,sucrose-sugar alcohol, sugar alcohol-sucrose, or sugar alcohol-sugaralcohol condensation products connected by ether linkages; and

c. reaction, by nucleophilic displacement, of the activated sucrose oractivated sugar alcohol with a reactive halogen, carboxylic acid, amine,or ester to form halogen-, carboxylic acid-, amino-, ester-, oranhydro-substituted sucrose, or halogen-, carboxylic acid-, amino-, orester-substituted sugar alcohols.

The experiments herein show that a facile or active group can beselectively added to one or more of the primary hydroxyl positions ofsucrose or sugar alcohols, by using a two-phase reaction in which thefacile-group reactant is dissolved in a water-immiscible solvent such astoluene and slowly added to an aqueous alkaline solution of sucrose orsugar alcohol. When TLC (thin layer chromatography) analysis of theaqueous layer shows that all of the sucrose or sugar alcohol has beenconsumed, TLC analysis of the solvent layer will show a single,UV-fluorescent carbohydrate derivative indicating that the reaction iscomplete. The presence of the activated sucrose or sugar alcohol canalso be determined by ¹³ C-NMR which also indicates that facile leavinggroups are positioned at specific primary hydroxyl positions.

The "activated sucrose" of the invention is demonstrated herein by theuse of a tosylation reaction and specifically the use of tosyl chloride.Tosyl is the preferred leaving group because of its low cost and readyavailability. However, other sulfonyl groups may be used in the reactionwith substantially the same results. Suitable sulfonyl derivatives thatwill form sulfonates with alcohols such as sucrose and sugar alcoholscomprise tosyl chloride, which yields tosylates; mesyl chloride (methylsulfonyl chloride) which yields methyl sulfonates or mesylates; trifylchloride, (α,α,α-trifluoromethyl sulfonyl chloride) which yieldstrifluoromethane sulfonates or trifylates; trimsyl chloride (mesitylenechloride or 2,4,6-trimethyl benzene sulfonyl chloride) which yield2,4,6-trimethyl benzene sulfonates or mesitylates; tripsyl chloride,(2,4,6,-triisopropyl benzene sulfonyl chloride) which yields2,4,6-triisopropyl benzene sulfonates or tripsylates; and1,1'-sulfonyldiimidazole, which yields imidazylates orimidazolesulfonates. In general, any sulfonyl derivative which isoperative under the conditions of the reaction may be used.

Non-sulfonyl substituents such as trityl may also be added to sucrose byreaction with trityl chloride.

It should be noted that sulfonyl, such as tosyl, and trityl derivativeshowever react by different mechanisms. Tosyl is a leaving group becauseit activates any hydroxyl group to which it is bonded during formationof the corresponding p-toluenesulfonyl ester. Trityl on the other hand,is not a leaving group and is not displaceable. The trityl groupprotects selected, generally primary, hydroxyl groups thus allowingother reactions to take place at non-tritylated hydroxyl groups withinthe molecule. Trityl can then be removed by acid to free the hydroxylgroup or groups to which it had been attached.

In a further embodiment, the 6,6'-di-O-tosyl sucrose is an activatedform of sucrose that can be used to synthesize specific sucroseanalogues by nucleophilic displacement of the tosyl groups, giving, forexample, 6,6'-dichloro-; 6,6'-dibromo-; 6,6'-di-iodo-; 6,6'-diamino-; 6,6'-dideoxy-; 6,6'-dicarboxymethyl sucrose and the like in high yield.The preparation of the tosyl sucrose derivative on a simple, but largescale, holds the potential for synthesizing a number of sucrosederivatives and analogues that would have variable uses as food bulkingagents and anticariogenic agents among others.

The activated intermediate sucrose products of the invention may becharacterized by the following formula: ##STR2## wherein X is a facileleaving group as indicated at the 6- and 6'-positions and preferably isa tosyl group or the like. As discussed herein, the groups other thantosyl are added to sucrose at its 6- and 6'-positions by nucleophilicdisplacement of the tosyl or similar groups.

As indicated above, the activated sucrose products of Formula 2 areintermediates ideally suited for production of a wide variety of sucrosecondensation products. Such sucrose products may be described by thegeneral formula: ##STR3##

In the above formula, R represents any organic moiety which can beattached to sucrose by displacement of the tosyl or equivalent groups atthe 6- and 6'-positions of "activated sucrose". Thus, each R group canbe another sucrose moiety (sucrose trimer), sugar alcohols such asglucitol or xylitol, or polysaccharides or their lower molecular weightanalogs (see High Molecular Weight Reaction Products section).

As noted, sucrose is the starting material when forming "activatedsucrose". However, various sugar alcohols may be used in place ofsucrose to form a series of "activated sugar alcohols" and theircorresponding reaction products. Such equivalent sugar alcohols includeglucitol, mannitol, xylitol, and the like.

According to this invention, it has been discovered that conducting thereaction of sucrose or various sugar alcohols with a sulfonyl derivativesuch as a tosyl halide as described herein, enables one to obtainspecificity of the reaction at the 6-and 6'-positions of sucrose or atone or both of the primary hydroxyl groups of the sugar alcohols. Theresulting products are sulfonyl substituted sucrose or sugar alcoholswherein a sulfonate, e.g., a tosyl ester, is substituted at the 6- and6'-positions of sucrose or at multiple methylene sites within thevarious sugar alcohols.

An especially novel feature of the invention concerns the method bywhich the sucrose or sugar alcohol products of the present invention areproduced. According to the invention, it has been discovered thatsucrose substituted at its 6- and 6'-positions, or sugar alcoholssubstituted at one or both of their primary hydroxyl groups, by asulfonyl derivative, e.g., tosyl, can be produced in high yield andpurity by conducting the reaction with two substantially immisciblesolvents. The process is conducted generally by dissolving theappropriate amount of sucrose or sugar alcohol in a slightly alkalineaqueous medium and then adding slowly thereto a sulfonyl halide such asa tosyl halide reactant contained in a substantially water-immiscibleorganic solvent. Organic solvents which may be used in the reactioncomprise such solvents as chlorinated aliphatic hydrocarbons such aschloroform and carbon tetrachloride; aromatic hydrocarbons such asbenzene, toluene, and xylene; and chlorinated aromatic hydrocarbons suchas chlorobenzene.

It should be understood that the process for reaction of sucrose or asugar alcohol with the reagents disclosed herein has wide applicabilityto the production of new sucrose and sugar alcohol reaction products.The concept of conducting the reaction at the interface of twosubstantially immiscible solvents containing the reactants provides anovel and effective procedure for producing the sucrose and sugaralcohol reaction products with the unexpected result of avoiding thesubstantial formation of unwanted products or by-products. The reactionis exemplified by the reactions and products described herein but is notlimited thereto.

In a preferred mode of conducting the reaction, the solution of thesulfonating agent in the organic phase is added slowly, preferablydropwise over a period of up to about one hour, to an aqueous alkalinesolution of sucrose or sugar alcohol to produce a derivative easilyrecovered from the aqueous phase. Further, the organic phase can beseparated and recycled for use in subsequent reactions.

Sucrose or specific sugar alcohol added to the aqueous phase is utilizedat a concentration of about 5 wt. % up to the limit of its solubility atthe temperature used. Ordinarily, a concentration of 5-50% by weight isemployed. Likewise, the reactant in the organic phase is employed at aconcentration of about 5 wt. % up to the limit of its solubility in thesolvent at the temperature used, but preferably using a concentration inthe range of 5-50 wt. %. To obtain specific derivatives, theconcentration may be varied by increasing the amount of organic solventand/or by decreasing the rate of dropwise delivery of the reactant tothe alkaline solution of sucrose or specific sugar alcohol.

While the ratios of reactants are ordinarily stoichiometric, the ratiosof organic phase reactant to sucrose, or sugar alcohol, may be variedfrom 1:2 to about 4:1, preferably about 1.2:1 to 2.2:1. Alkali isprovided at a concentration of 0.05 to 5 molar, preferably 0.1 molar.The reaction takes place in a relatively short period of time, such asone half hour to 3 hours. However, occasionally the reaction is allowedto continue overnight. This is possible because room temperature issuitable for conducting the reaction, although 0° to 80° C., preferably5° to 50° C., is also useful.

The process of the invention results in the production of an "activatedsucrose" or "activated sugar alcohols" which contain facile leavinggroups at the 6- and 6'-positions of sucrose or the primary alcoholpositions of the reacted sugar alcohol. In a preferred embodiment, asulfonyl group such as a tosyl group is selectively added to the 6- and6'-positions of sucrose by using the said two-phase reaction in whichtosyl chloride is dissolved in a solvent such as toluene and addedslowly to the aqueous, alkaline solution of sucrose. As indicated, thisreaction results in sucrose substituted at its 6- and 6'-positions bytosyl groups. Tosyl is the preferred substituent because of economicsand availability, but it is clear from the description herein that otheractive sulfonyl derivatives such as mesyl chloride or the like can beemployed in the reaction. However, the availability and low costs oftosyl chloride make it eminently suitable for the reaction of theinvention.

In an important further embodiment of the invention, the activatedsucrose containing tosyl groups at its 6- and 6'-positions isexceedingly useful as an intermediate to synthesize new sucrosecondensation products. Such new products include dianhydrosucrose,sucrose dimers and trimers, and sucrose linked to carbohydrates ofvarying molecular configurations and of varying molecular weights up toand including polysaccharides.

Similar condensations may be obtained by adding 6,6'-di-O-tosyl sucrose,i.e., "activated sucrose " (dissolved in a solvent such as toluene), toan aqueous, alkaline solution of other carbohydrates, such as sugaralcohols. Depending on the ratio of sugar alcohol to 6,6'-di-O-tosylsucrose, two different types of products are obtained. A 1:1 ratio ofsugar alcohol to 6,6'-di-O-tosyl sucrose gives preference to theformation of a cyclic 6,6'-sugar alcohol-sucrose, and a 2:1 ratio givespreference to the formation of a linear 6,6'-di-O-sugar alcohol-sucrose.

In a similar manner, primary alcohol groups of sugar alcohols may beactivated by the addition of tosyl groups following dropwise addition oftosyl chloride in a solvent such as toluene to aqueous, alkalinesolutions of sugar alcohols. The 1,6-di-O-tosyl-alditols, e.g.,glucitol, or corresponding 1,5-di-O-tosyl-pentitols, e.g., xylitol,dissolved in toluene, added to an aqueous, alkaline solution of sucrose,provides displacement of the tosyl groups and condensation of sucrosewith the two primary alcohol ends of the alditol or pentitol.

In a particularly preferred embodiment of the invention, 6,6'-di-o-tosylsucrose can be specifically converted, in high yield and purity, into3,6;3',6'-dianhydrosucrose by refluxing the tosyl sucrose in ananhydrous lower alkyl alcohol, e.g. dry methanol, with catalytic amountsof an alkali methyl alkoxide, e.g., sodium methoxide. The reactionproduces high conversion into 3, 6; 3',6'-dianhydrosucrose that can becrystallized.

When the same reaction is conducted at a temperature of about 60° C., arelatively large yield of 3,6;3',6'-dianhydrosucrose in high purity isobtained in the aqueous phase, along with smaller amounts of twomonoanhydrosucroses, presumably 3,6-anhydrosucrose and3',6'-anhydrosucrose. These three anhydrosucrose compounds can beseparated on a silica gel column, using the filtering column technique.The first fractions contain carbohydrate, corresponding by TLC to3,6;3',6'-dianhydrosucrose. This compound crystallizes when the firstfractions of column eluant are pooled.

When 6,6'-di-O-tosyl sucrose, the compound obtained in the toluene phaseat 20° C., is dissolved in methanol with the addition of a catalyticamount of sodium methoxide and the solution refluxed for 24 hours, asingle carbohydrate results, as judged by TLC. This compound migrates atthe same position on TLC as the 3,6;3',6'-dianhydrosucrose produced inthe aqueous, alkaline phase of the 60° C. reaction. This compound,derived from 6,6'-di-O-tosyl sucrose, can be crystallized from analcohol, preferably ethanol. The form of the crystals is the same asthat of the crystals formed in the column chromatography eluant.

Each of the compounds, that is, the one recovered from the aqueous phaseof the 60° C. reaction of tosyl chloride in toluene with an aqueoussolution of sucrose, and the one recovered from refluxing6,6'-di-O-tosyl sucrose in methanol/sodium methoxide, have specificoptical rotation of +6.8° in water. Further, neither of the reactionsaffords a product which is oxidized by sodium periodate.

In the known prior art [Lemieux and Barrette, Canadian Journal ofChemistry, vol. 37 (1959) 1964-1969 and Bolton, et al., CarbohydrateResearch, vol. 21 (1972) 133-143] dianhydrosucrose has been reported.However, according to said prior art, the dianhydrosucrose has beenproduced neither in pure form nor in any large quantities. Thus, theproduction of 6,6'-di-O-tosyl sucrose, in the two-phase reaction of theinvention, is ideal to form 3,6;3',6'-dianhydrosucrose in asubstantially pure form, in high yields, and in large quantities.

3,6;3',6'-Dianhydrosucrose is a nonmetabolizable bulking agent,retaining many of the properties of sucrose. Its structure is depictedas follows: ##STR4##

Several different types of sucrose and sugar alcohol products arecontemplated by this invention: (1) synthesis of a specific tosylatedsucrose, e.g., 6,6'-di-O-tosyl sucrose; (2) synthesis of specifictosylated sugar alcohols, e.g., 1,6-di-O-tosyl glucitol; (3) synthesisof sucrose condensed with sucrose and linked together by ether linkagesto give a trimer, denominated "sucrotriose"; (4) reaction of sugaralcohols with "activated sucrose" to link sugar alcohols to sucrose atits C-6 and C-6' positions by ether bonds to give both cyclic 6,6'-sugaralcohol-sucroses and linear 6,6'-di-O-sugar alcohol sucroses; (5)reaction of a 1,6-di-O-tosyl alditol or a corresponding 1,5-di-O-tosylpentitol with sucrose to give sucrose attached to the alditol orpentitol by ether linkages between positions 6 or 6' of sucrose andeither primary hydroxyl group of the alditol or pentitol; (6) reactionof a 1,6-di-O-tosyl alditol or a corresponding 1,5-di-O-tosyl pentitolwith a variety of sugar alcohols to link the selected sugar alcohol byether bonds between either primary hydroxyl group of the selected sugaralcohol and either primary hydroxyl group of the di-O-tosylated alditolor pentitol; and (7) synthesis of specific anhydrosucrose products,e.g., 3,6;3',6'-dianhydrosucrose.

As indicated above, the "activated sucrose" and "activated sugaralcohols" of the invention contain facile leaving groups, such as tosyl,and are eminently suitable for reaction with a wide array of reactantsto produce a range of substituted sucrose and sugar alcohol products.Thus, in one embodiment, "activated sucrose" may be reacted with variousreagents to form, by nucleophilic displacement, a series of new sucroseproducts which contain 6- and 6'-substituents such as Cl, Br, I, NH₂,OCH₂ COOH, OOCR, and H. These sucrose products are formed by reaction of"activated sucrose" with reagents such as sodium chloride to substitutechloride groups at the 6- and 6'-positions in high yield and goodpurity. Similar reactions may be conducted with sodium bromide, sodiumiodide, ammonia, acetic acid, or the like. This results in a pathway bywhich multiple substituted sucrose products can be produced.

Additional objects and advantages of the present invention will becomereadily apparent to those skilled in the art from the following exampleswhich exemplify the low molecular weight products of this invention andtheir methods of preparation. As will be realized, the invention iscapable of other and different embodiments, and its several details arecapable of modifications in various obvious respects, all withoutdeparting from the invention.

EXAMPLE 1

Synthesis of 6,6'-di-O-tosyl sucrose

Sucrose (10 g, 29.2 mmol) was dissolved in 50 mL of 0.1 M NaOH. Tosylchloride (12.3 g, 64.2 mmol) was dissolved in 50 mL of toluene and addedto the sucrose solution over 30 minutes at 22°. The pH of the reactionwas maintained between 7 and 8. The 6,6'-di-O-tosyl sucrose migratesinto the toluene phase where it is detected by TLC analysis [one ascentin methyl cyanide/water (85/15, v/v) on Whatman K5 plates] as aUV-fluorescent compound that also gives a carbohydrate stain when theTLC plate is dipped into a solution containing 0.3% (w/v)N-(1-naphthyl)ethylene diamine and 5% (v/v) concentrated sulfuric acidin methanol, followed by drying and heating at 120° C. for 10 minutes.The toluene phase was rotary evaporated to give a syrup containing theproduct.

EXAMPLE 2

Reaction of sucrose with 6,6'-di-O-tosyl sucrose

Sucrose (10 g, 29.2 mmol) was dissolved in 100 mL of 0.1 M NaOH.6,6'-Di-O-tosyl sucrose (7 g, 14.6 mmol) was then dissolved in 100 mL oftoluene and added to the aqueous sucrose solution over 30 minutes at 22°C. The product, a sucrose trimer denominated sucrotriose, appeared inthe aqueous phase. TLC of the aqueous and toluene phases is performed aspreviously described to verify product formation and location.

EXAMPLE 3

a. Preparation of 3,6;3',6'-dianhydrosucrose

Crystalline 6,6'-di-O-tosyl sucrose (8.3 g, 17.3 mmol) was dissolved in200 mL of dry methanol. The temperature was slowly increased until thesolution began to reflux and sodium methoxide (1.75 g, 32.4 mmol) wasadded in small portions over 30 minutes. The solution was refluxed 24hours. TLC [one ascent in acetonitrile/water (85:15, v/v) on Whatman K5plates] showed one compound. Water (200 mL) is added and the solutionrotary evaporated to a syrup under vacuum at 350C. The syrup wasredissolved in 150 mL of water and neutralized with 0.1 M HCl, treatedwith charcoal (2 g) and filtered. The filtrate was rotary evaporated toa solid and dissolved in 200 mL of warm ethanol and filtered; theremaining solid (primarily salts) was treated with 100 mL of dryethanol. The ethanol extracts are combined and rotary evaporated to asolid, which is the 3,6;3',6'-dianhydrosucrose. This solid was dissolvedin a minimum amount of hot ethanol, and crystals obtained.

6,6'-Di-O-tosyl sucrose (2 g, 4.2 mmol) was dissolved in 50 mL ofmethanol and sodium methoxide (350 mg, 6.5 mmol) added. The solution wasallowed to reflux for 24 hours. TLC analysis (10 cm Whatman KS plateswith one ascent in acetonitrile/water, 85:15 v/v) showed a singlecompound migrating in the same location as 3,6;3',6'-dianhydrosucrose.The methanol solution was rotary evaporated to a syrup, which wasdissolved in water, filtered and neutralized with a small volume of 1 MHCl. The aqueous solution was rotary evaporated to a syrup, which wasdissolved in methanol and warmed; the insoluble material (salts) wasremoved by filtration. The solution was rotary evaporated to a syrup.The syrup was dissolved in 100 mL hot ethanol and concentrated to avolume of 50 mL. Crystals start to form in 12 hours at room temperature.The crystals are dissolved in water before TLC analysis and measurementof the specific optical rotation.

b. Separation of anhydrosucroses by silica gel, filtering columnchromatography

The mixture of anhydrosucroses present in the aqueous phase of the abovereaction following its rotary evaporation to a syrup was washed severaltimes with acetone before a final wash with ethanol to give a solid,anhydrous powder. Approximately 10 g of this solid was dissolved in10-15 mL of water. Solid silica gel (500 mg) was added, and the mixturerotary evaporated to remove the free water. This silica gel-carbohydrateadsorbed material was added to the top of a silica gel column (5.5×30cm), and the compounds eluted (100-mL fractions) with differentproportions of acetonitrile/water: 100:0 (1L); 99:1 (2L); 98:2 (1L); and96:4 (2L). 3, 6;3',6'-Dianhydrosucrose was recovered from the 96:4eluant. On standing at room temperature (20°-21° C.), the compoundcrystallized in the pooled 96:4 eluant. Specific optical rotation wasmeasured, and a TLC analysis performed.

EXAMPLE 4

Synthesis of sucrose-sugar alcohol compounds from sugar alcohol and6,6'-di-O-tosyl sucrose.

a. 1:1 Ratio of sugar alcohol to 6,6'-di-O-tosyl sucrose using thealditol, D-glucitol, as the example.

D-Glucitol (also known as D-sorbitol) (10 g, 55 mmol) was dissolved in50 mL 0.1M NaOH; 6,6'-di-O-tosyl sucrose (26.5 g, 55 mmol) was dissolvedin 50 mL toluene and added to the aqueous D-glucitol solution over 30minutes at 22° C. Reaction progress was monitored and confirmed by TLC.Although D-glucitol was used as the example, other alditols, such asD-mannitol, and pentitols, such as D-xylitol, may be substituted forD-glucitol. The reaction is shown as follows: ##STR5## whereTs=p-toluenesulfonyl.

Formula 5. Synthesis of 6,6'-D-glucitol sucrose.

b. 2:1 Ratio of sugar alcohol to 6,6'-di-O-tosyl sucrose using thealditol, D-glucitol, as the example.

D-Glucitol (10 g, 55 mmol) was dissolved in 50 mL 0.1 M NaOH;6,6'-di-O-tosyl sucrose (13.3 g, 27.6 mmol) was 5 dissolved in 50 mLtoluene and added to the aqueous D-glucitol solution over a period of 30minutes at 22° C. TLC was performed as before. The reaction is shown asfollows: ##STR6## where Ts=p-toluenesulfonyl

Formula 6. Synthesis of 6,6'-di-O-D-glucitol sucrose.

EXAMPLE 5

Synthesis of 1,6-di-O-tosyl-D-glucitol.

D-glucitol (10 g, 55 mmol) was dissolved in 100 mL of 0.1 M NaOH. Tosylchloride (23.3 g, 121 mmol) was dissolved in 100 mL of toluene and addedto the aqueous D-glucitol solution over 30 minutes at 22° C. Thereaction was monitored by TLC using the method described above. The1,6-di-O-tosyl D-glucitol appeared in the toluene phase and wasUV-fluorescent on TLC plates. The reaction was permitted to proceed for18 hours at 22° C. Although D-glucitol was used as the example, otheralditols, such as D-mannitol, and pentitols, such as D-xylitol, may besubstituted for D-glucitol.

EXAMPLE 6

Synthesis of 1,6-di-O-sucro D-glucitol.

Sucrose (20 g, 58.4 mmol) was dissolved in 100 mL of 0.1M NaOH.1,6-Di-O-tosyl D-glucitol (14.4 g, 29.2 mmol) was dissolved in 100 mL oftoluene and added to the aqueous sucrose solution over 30 minutes at 22°C. The product was soluble in the aqueous phase. The reaction waspermitted to proceed for 18 hours, being monitored by TLC. AlthoughD-glucitol was used as the example, other alditols, such as D-mannitol,and pentitols, such as D-xylitol, may be substituted for D-glucitol.

EXAMPLE 7

Synthesis of 4,1'-dichloro-4,1'-dideoxy-galacto-sucrose.

6,6'-Di-O-tosyl sucrose (20 g, 31 mmol) was treated with sulfurylchloride in chloroform and pyridine to form4,1'-dichloro-4,1'-dideoxy-6,6'-di-O-tosyl-galacto-sucrose. This wasreacted with aqueous sodium hydroxide to the corresponding4,1'-dichloro-4'-dideoxy-galacto-sucrose.

EXAMPLE 8

Synthesis of 6,1',6'-tri-O-trityl sucrose.

Sucrose (25 g, 73 mmol) was dissolved in 250 mL of 1M NaOH. tritylchloride (46 g, 165 mmol) was dissolved in 250 mL of toluene and addedslowly over 5 hours at 22° C. to the sucrose solution with constantstirring. The reaction was stirred at 22° C. for an additional 12 hours.The pH of the reaction was maintained between 7 and 9, with the optimumat 8, by the addition of aqueous NaOH (20% w/v). The toluene phase wasseparated from the alkaline phase and washed with 100 mL of water. TLC[one ascent in methanol/acetone/water/chloroform (20:20:3:57 v/v/v/v),Whatman K5 plate] of the toluene phase indicated one, fast migratingcompound with an R_(f) corresponding to 6,1',6'-tri-O-trityl sucrose.(See Otake, Bull. Chem. Soc. Japan 43: 3199, 1970). The toluene layerwas dried with anhydrous sodium sulfate, filtered, and rotary evaporatedat 50° C. to a solid 35.3 g). Only one compound was shown by TLC,indicating a high yield and a high degree of purity.

EXAMPLE 9

Synthesis of chloro-deoxy-galacto-sucrose products.

a. 6,1',6'-Tri-O-trityl-2,3,4,3',4'-penta-O-acetyl sucrose.

6,1',6'-Tri-O-trityl sucrose (30g, 28 mmol; TTS) dissolved in 480 mL ofanhydrous pyridine. Acetic anhydride (300 mL) was added, and thesolution was stirred for 20 hours at 22° C. The reaction solution waspoured under vigorous stirring into 3 L of ice-water containing 153 mLof acetone, and stirred until all the ice was melted. A whiteprecipitate was formed and recovered by filtration. The recoveredprecipitate was washed with water (5×20 mL) and dried under vacuo at 40°C. to give 29.4 g of pure, fully acetylated TTS.

b. 2,3,6,3',4'-Penta-O-acetyl sucrose.

Fully acetylated TTS (10 g, 8 mmol) was dissolved in 250 mL of glacialacetic acid. The solution was heated to boiling and 5 mL of water wereadded. The solution was allowed to reflux for 30 minutes. After coolingto 22° C., the reaction mixture was filtered and rotary evaporated at50° C. to remove the acetic acid. Pure, 2,3,6,3',4' -penta-O-acetylsucrose (9.4 g) was recovered. During detritylation, the acetyl group atposition-4 migrates to position-6 (see Formula 1).

C.2,3,6,3',4'-Penta-O-acetyl-4,1',6'-trichloro-4,1',6'-trideoxy-galacto-sucrose.

2,3,6,3',4'-Penta-O-acetyl sucrose (9 g, 16 mmol) was dissolved in amixture of pyridine (250 mL) and chloroform (30 mL), previously cooledto -78° C., in an acetone-dry ice bath. Sulfuryl chloride (27 mL),previously cooled to -78° C., was added dropwise under vigorous stirringover a 45-minute period. The stirring reaction was maintained at -78° C.for 2 hours, allowed to warm to 22° C., and stirred for an additional 48hours. TLC [one ascent in chloroform/ethanol (30:1 v/v), Whatman K5Fplate] indicated one major, fast migrating product. The pyridinesolution was rotary evaporated to give2,3,6,3',4',-penta-O-acetyl-4,1',6'-trichloro-4,1',6'-trideoxy-galacto-sucrose.Authenticity of the recovered product was determined by proton-decoupled¹³ C-NMR. Reaction of 2,3,6,3',4'-penta-O-acetyl sucrose with sulfurylchloride in pyridine to synthesize the trichloro derivative wasaccompanied by inversion of the pyranose portion of sucrose from a glucoto a galacto configuration.

d. 4,1',6'-Trichloro-4,1',6',-trideoxy-galacto-sucrose.

2,3,6,3',4'-Penta-O-acetyl-4,1',6'-trichloro-4,1',6'-trideoxy-galacto-sucrose(6.3 g, 10 mmol) was dissolved under stirring in methanol (300 mL)sodium methoxide (0.6 g) was added, and the reaction was stirred at 22°C. for 10 hours. Deacetylation with sodium methoxide in methanolafforded 4,1',6'-trichloro-4,1',6'-trideoxy-galacto-sucrose(Sucralose™).

EXAMPLE 10

Synthesis of 4-Chloro-4-deoxy-galacto-sucrose.

In a manner similar to Example 9(c) above, 6,1',6'-tri-O-trityl sucrosewas reacted with sulfuryl chloride in a pyridine-chloroform solution andin the presence of an acid. 4-Chloro-4-deoxy-galacto-sucrose wasrecovered as a pure product.

It has been shown [Hough and Khan, Trends in Biological Science, vol. 3(1978) 61-63] that the monochloro sucrose derivative is four timessweeter than sucrose, the dichloro derivative is 600 times sweeter thansucrose, and the trichloro derivative is 2000 times sweeter thansucrose.

High Molecular Weight Reaction Products

By use of the same two-phase reaction system, the processes of thepresent invention in a major embodiment produce "activatedoligosaccharides" and "activated polysaccharides" which have sulfonylfacile leaving groups such as tosyl at the activated primary hydroxylpositions. Because of the relatively low cost and ready availability oftosyl chloride, tosyl is the most economical facile leaving group. Whilethe reaction is effective with nonreducing carbohydrates in general, thepresent invention is described herein with respect to oligosaccharidesor polysaccharides as the preferred starting materials.

This embodiment of the invention provides a procedure by which some ofthe primary alcohol groups within oligosaccharides or polysaccharidescan be activated or made reactive in a specific manner so that a wideseries of new oligosaccharide or polysaccharide products can beproduced. The new products contain ether linkages so that the newproducts are useful as food and non-food agents which require propertiescharacteristic of polysaccharides or their lower molecular weightanalogs. Substituting sucrose and/or sugar alcohols ontopoly-saccharides such as amylose and cellulose increases theirwater-solubility so that the resulting polysaccharide products are moreuseful as fibers, gels, gums, and films for foods and pharmaceuticals.

The present invention provides three significant new types of products,i.e.,

a. activated polysaccharides by substitution of a sulfonyl group on oneor more of the primary alcohols within the reacted polysaccharide;

b. reaction of the activated polysaccharide with sucrose or withdifferent sugar alcohols to form polysaccharide-sucrose orpolysaccharide-sugar alcohol condensation products connected by etherlinkages; and

c. reaction, by nucleophilic displacement, of the activatedpolysaccharide with a reactive halogen, carboxylic acid, amine, or esterto form halogen-, carboxylic acid-, amino-, or ester-substitutedpolysaccharides.

The experiments herein show that a facile or active group can beselectively added to various primary methylene positions inoligosaccharides or polysaccharides, by using a two-phase reaction inwhich the facile-group reactant is dissolved in a water-immisciblesolvent such as toluene and slowly added to an aqueous alkaline solutionof oligosaccharide or polysaccharide. When TLC analysis shows that allof the starting material has been consumed, TLC analysis will show asingle, UV-fluorescent carbohydrate derivative indicating that thereaction is complete.

The "activated oligosaccharide" or "activated polysaccharide" of theinvention is demonstrated herein by the use of a tosylation reaction andspecifically the use of tosyl chloride. Tosyl is the preferred leavinggroup because of its low cost and ready availability. However, othersulfonyl halides such as mesyl chloride may be used in the reaction withsubstantially the same results as is discussed above with respect to thelow molecular weight products of this invention.

In this embodiment, the poly-6-O-tosyl saccharides are activated formsthat can be used to synthesize specific analogues by nucleophilicdisplacement of the sulfonyl groups, giving, for example,poly-6-chloro-; poly-6-bromo-; poly-6-iodo-; poly-6-amino-;poly-6-deoxy-; poly-6-carboxymethyl derivatives of oligo- andpolysaccharides in high yield. The preparation of poly-tosyl oligo- orpolysaccharide on a simple, but large scale, holds the potential forsynthesizing a number of derivatives and analogues that would havevariable uses as food and non-food ingredients.

As noted in the previous section, sucrose and various sugar alcohols arethe starting materials when forming "activated sucrose" and "activatedsugar alcohols", respectively. However, various oligo- orpolysaccharides may be used in place of sucrose or sugar alcohols toform a series of "activated oligosaccharides" or "activatedpolysaccharides". Such equivalent saccharides consist of thecyclodextrins, cellulose, amylose, amylopectin, pullulan, chitosan andthe like. Since these equivalent polysaccharides are usually insolublein aqueous media, a pyridine solution is used to expedite the reactionsas described hereinafter.

As noted in the previous section, the R group of Formula 3 can be apolysaccharide, e.g., amylose, cellulose, amylopectin, chitosan,pullulan, the cyclodextrins, etc., or their lower molecular weightanalogs.

According to this invention, it has been discovered that conducting thereaction of oligosaccharides or polysaccharides with a sulfonyl groupsuch as a tosyl halide as described herein, enables one to obtainspecificity of the reaction at multiple primary hydroxyl groups withinthe oligo- or polysaccharide. The resulting products arepoly-tosyl-substituted reaction products wherein tosyl or other sulfonylgroups are substituted at multiple methylene sites within theoligosaccharide or polysaccharide.

An especially novel feature of the invention concerns the method bywhich the oligo- and polysaccharide products of the present inventionare produced. According to the invention, it has been discovered thatoligo- and polysaccharides substituted at multiple primary hydroxylpositions by e.g., tosyl groups, can be produced in high yield andpurity by conducting the reaction with two substantially immisciblesolvents. The process is conducted generally by dissolving theappropriate amount of oligosaccharide or polysaccharide in a slightlyalkaline aqueous medium and then adding slowly thereto a sulfonylreactant, such as a tosyl chloride, contained in a substantiallywater-immiscible organic solvent. Organic solvents which may be used inthe reaction comprise such solvents as chlorinated aliphatichydrocarbons such as chloroform and carbon tetrachloride; aromatichydrocarbons such as benzene, toluene, and xylene; and chlorinatedaromatic hydrocarbons such as chlorobenzene.

It should be understood that the process for reaction of oligo- orpolysaccharides with the reagents disclosed herein has wideapplicability to the production of new reaction products. The concept ofconducting the reaction at the interface of two substantially immisciblesolvents containing the reactants provides a novel and effectiveprocedure for producing the high-molecular-weight saccharide reactionproducts with the unexpected result of avoiding the substantialformation of unwanted products. The reaction is exemplified by thereactions and products described herein but is not limited thereto.

In a preferred mode of conducting the reaction, the solution of thesulfonating reagent, e.g., tosyl chloride, in the organic phase is addedslowly, preferably dropwise, over a period of up to about one hour, toan aqueous alkaline solution of oligo- or polysaccharide to produce aderivative easily recovered from the aqueous phase. Further, the organicphase can be separated and recycled for use in subsequent reactions.

The oligo- or polysaccharide added to the aqueous phase is utilized at aconcentration of about 5 wt. % up to the limit of its solubility at thetemperature used. Ordinarily, a concentration of 5-50% by weight isemployed. Likewise, the reactant in the organic phase is employed at aconcentration of about 5 wt. % up to the limit of its solubility in thesolvent at the temperature used, but preferably using a concentration inthe range of 5-50 wt. %. To obtain specific derivatives, theconcentration may be varied by increasing the amount of organic solventand/or by decreasing the rate of dropwise delivery of the reactant tothe alkaline solution of oligosaccharide or polysaccharide.

While the ratios of reactants are ordinarily stoichiometric, the ratiosof organic phase reactant to oligo- or polysaccharide may be varied from1:2 to about 4:1, preferably about 1.2:1 to 2.2:1. Alkali is provided ata concentration of 0.05 to 5 molar, preferably 0.1 molar. The reactiontakes place in a relatively short period of time, such as one half hourto 3 hours. However, occasionally the reaction is allowed to continueovernight. This is possible because room temperature is suitable forconducting the reaction, although 0° to 80° C., preferably 5° to 50° C.,is also useful.

The process of the invention results in the production of an "activatedoligosaccharide" or an "activated polysaccharide" which contains facileleaving groups at multiple primary hydroxyl positions of the reactedoligo- or polysaccharide. In a preferred embodiment, a tosyl group isselectively added to multiple primary hydroxyl positions of oligo- orpolysaccharides by using said two-phase reaction in which tosyl chlorideis dissolved in a solvent such as toluene and added slowly to theaqueous, alkaline solution of high-molecular-weight saccharide. Asindicated, this reaction results in substitution at multiple methylenepositions by tosyl groups. Tosyl is the preferred substituent because ofeconomics and availability, but it is clear from the description hereinthat other active materials such as mesyl chloride or the like can beemployed in the reaction. However, the availability and low costs oftosyl chloride makes it eminently suitable for the reaction of theinvention.

In an important further embodiment of the invention, the activatedoligosaccharide or the activated polysaccharide containing tosyl orsimilar groups at multiple primary hydroxyl positions is eminentlyuseful as an intermediate to synthesize new oligo- or polysaccharidecondensation products.

Experiments have shown that several poly-6-O-tosyl-polysaccharides(e.g., cellulose, amylose, amylopectin, pullulan, chitosan) andpoly-6-O-tosyl oligosaccharides (e.g., the cyclodextrins) can be formedand are insoluble in both the aqueous and organic phases. They are,however, soluble in pyridine. Therefore, in this reaction, an aqueous,alkaline solution of sucrose is added to a pyridine solution of thepoly-6-O-tosyl-polysaccharide or the poly-6-O-tosyl oligosaccharide. Thesucrose will displace the tosyl groups to give a polysaccharide oroligosaccharide chemically bonded to the 6- or 6'-positions of sucroseby ether linkages at its primary methylene sites originally bearing thetosyl groups.

In a similar manner, sugar alcohols may be added to an "activatedoligosaccharide" or an "activated polysaccharide". The selected sugaralcohol will displace the tosyl groups in the poly-tosylated startingmaterial to give a product in which the selected sugar alcohol ischemically bonded at either of its primary hydroxyl positions by etherlinkages at the primary methylene sites originally bearing the tosylgroups.

Several different types of high-molecular-weight-saccharide products arecontemplated by this invention: (1) synthesis of sulfonyl substitutedpoly-saccharides, e.g., poly-6-O-tosyl amylose, or their lower molecularweight analogs; (2) reaction of poly-tosylated polysaccharides, or theirlower molecular weight analogs, with sucrose to give high molecularweight products in which sucrose is attached by ether linkages betweeneither position 6 or 6' of sucrose and the primary methylene positionsat which the tosyl groups were originally bonded; (3) reaction ofpoly-tosylated polysaccharides, or their lower molecular weight analogs,with sugar alcohols to give high molecular weight products in whichsugar alcohols are attached by ether linkages between either primaryhydroxyl position of the sugar alcohol and the primary methylenepositions at which the tosyl groups were originally bonded; and (4)synthesis of sulfonyl substituted oligosaccharides, e.g.,β-cyclodextrin, for reaction with sucrose and/or sugar alcohols asdescribed in (2) and (3) above.

As indicated above, the "activated oligosaccharides" and "activatedpolysaccharides" of the invention contain facile leaving groups, such astosyl or mesyl, and are eminently suitable for reaction with a widearray of reactants to produce a range of substituted products.

EXAMPLE 9

Synthesis of poly-6-O-tosyl polysaccharides and their reaction withsucrose.

a. Synthesis of poly-6-O-tosyl cellulose.

Alpha-cellulose or micro-crystalline cellulose (10 g, 62 mmolanhydroglucose) was dissolved in 20 mL Cadoxen (5% cadmium oxide in 28%aqueous ethylenediamine). After dissolution (ca. 15 minutes), theCadoxen-cellulose solution was diluted with water to 100 mL. Tosylchloride (4 g, 20.7 mmol) was dissolved in 100 mL of toluene and addedto the Cadoxen-cellulose solution over 30 minutes at 22° C. Tosylcellulose became insoluble in both the aqueous and organic phases.Samples of tosyl cellulose are obtained by centrifugation of the aqueousphase followed by dissolution in pyridine. The reaction was monitored bydetermining the amount of UV-fluorescence on a TLC plate. The maximumUV-fluorescence indicates the maximum synthesis of tosyl cellulose.##STR7## where Ts=p-toluenesulfonyl

Formula 7. Preparation of poly-6-O-tosyl cellulose.

b. Synthesis of poly-6-0-tosyl amylose.

Amylose (10 g, 62 mmol anhydroglucose) was dissolved in 10 mL dimethylsulfoxide (DMSO) under stirring and gentle warming (ca. 50° C.). Afterdissolution, the DMSO-amylose solution was diluted with 0.1 M NaOH to100 mL. Tosyl chloride (4 g, 20.7 mmol) was dissolved in 100 mL oftoluene and added to the aqueous amylose solution over 30 minutes at 22°C. Tosyl amylose becomes insoluble in both the aqueous and organicphases. Tosyl amylose, obtained by centrifugation of the aqueous phase,was dissolved in pyridine. The reaction was monitored by determining theamount of UV-fluorescence by TLC. The maximum UV-fluorescence indicatesthe maximum synthesis of tosyl amylose. The reaction is similar to thatof forming the poly-6-O-tosyl cellulose.

c. Synthesis of poly-6-O-tosyl amylopectin, pullulan, and chitosan.

Each of these polysaccharides (10 g) was dissolved in 100 mL of 0.1 MNaOH. Tosyl chloride (4 g, 20.7 mmol) was dissolved in 100 mL of tolueneand added to the aqueous polysaccharide solutions over 30 minutes at 22°C. Each tosyl polysaccharide becomes insoluble in both the aqueous andorganic phases. A sample of each tosylated polysaccharide was obtainedby centrifugation of the aqueous phase followed by dissolution inpyridine. The reaction was monitored by determining the amount ofUV-fluorescence by TLC. The maximum UV-fluorescence demonstrated thatmaximum synthesis of the tosyl polysaccharide has taken place.

d. Attachment of sucrose to each of the poly-6-O-tosyl polysaccharides.

Poly-6-O-tosyl polysaccharide (12-14 g, d.s.=0.24-0.33) was dissolved in100 mL of pyridine. Sucrose (5 g, 14.6 mmol) was dissolved in 100 mL of0.1 M NaOH and added to the poly-6-O-tosyl polysaccharide-pyridinesolution over 30 minutes at 50° C. Reaction progress was monitored byTLC by relating the consumption of sucrose with the loss of fluorescenceat the origin using the method described above. The poly-6-O-sucropolysaccharides are soluble in the aqueous-pyridine solution. They arerecovered by the addition of two volumes of ethanol. The reaction shownbelow is for the formation of poly-6-O-sucro-cellulose, but similarequations may be written for amylose, amylopectin, pullulan andchitosan, and their lower molecular weight analogs, and for thecyclodextrins. ##STR8## where Ts=p-toluenesulfonyl

Formula 8. Preparation of poly-6-O-sucro-cellulose.

The invention has been described herein with reference to certainpreferred embodiments. However, as obvious variations thereon willbecome apparent to those skilled in the art, the invention is not to beconsidered as limited thereto.

What is claimed is:
 1. Sucrose linked through its 6- or 6'-positions to one or more primary hydroxyl group of sugar alcohols, sucrose, cyclodextrins, or polysaccharides or their lower molecular weight analogs.
 2. A sucrose according to claim 1 which is linked to a primary hydroxyl position of a sugar alcohol selected from the group consisting of the alditols and pentitols.
 3. A sucrose according to claim 1 which is a sucrose trimer.
 4. A sucrose according to claim 1 linked through its 6- or 6'-positions to multiple primary hydroxyl groups of cyclodextrins.
 5. A sucrose according to claim 1 linked through its 6- or 6'-positions to multiple primary hydroxyl groups of polysaccharides selected from the group consisting of cellulose, amylose, amylopectin, chitosan and pullulan, and their lower molecular weight analogs.
 6. A sucrose according to claim 2 which is a cyclic 6,6'-sugar alcohol-sucrose, where the sugar alcohol is selected from the group consisting of alditols and the pentitols.
 7. A sucrose according to claim 2 which is a linear 6,6'-di-O-sugar alcohol-sucrose, wherein the sugar alcohol is selected from the group consisting of the alditols and the pentitols.
 8. A process for the preparation of a series of alditol or pentitol sugar alcohol-sucrose products which comprises slowly adding 6,6'-di-O-tosyl sucrose in a substantially water-immiscible organic solvent to a pentitol or an alditol sugar alcohol in an alkaline solution of the sugar alcohol, wherein a reaction takes place at the interface of the alkaline solution and the organic solution, and maintaining the reaction until the alditol or pentitol sugar alcohol-sucrose product is produced.
 9. The process of claim 8, wherein the organic solvent containing 6,6'-di-O-tosyl sucrose is added to aqueous sugar alcohol solution in a dropwise manner.
 10. The process of claim 8, wherein the organic solvent is a chlorinated organic solvent or an aromatic solvent.
 11. The process of claim 8, wherein the organic solvent is selected from the group consisting of methylene chloride, chloroform, carbon tetrachloride, benzene, toluene, or a xylene.
 12. The process of claim 8, wherein the sugar alcohol is present in the alkaline aqueous solution in a concentration of about 5% by weight up to the limit of solubility of the sugar alcohol in water.
 13. The process of claim 8, wherein the concentration of 6,6'-di-O-tosyl sucrose in the water-immiscible organic solvent is from about 5% by weight up to the limit of solubility of the 6,6'-di-O-tosyl sucrose in the solvent.
 14. The process of claim 8, wherein the molar ratio of 6,6'-di-O-tosyl sucrose in the organic phase reactant to sugar alcohol reactant in the aqueous solution is from about 1:1 to about 1:4.
 15. The process of claim 8, wherein the reaction is conducted at a temperature in a range of about 0° to about 80° C.
 16. The process according to claim 15, wherein the molar ratio of 6,6'-di-O-tosyl sucrose to sugar alcohol is about 1:1 to about 1:1.1, the reaction is conducted at a temperature of about 15° to about 25° C., and at a pH of about 7.5 to about 10.5, and the organic solution of the 6,6'-di-O-tosyl sucrose reactant is added to the sugar alcohol solution over a period of about 15 to about 45 minutes.
 17. The process according to claim 15, wherein the molar ratio of 6,6'-di-O-tosyl sucrose to sugar alcohol is about 1:1 to about 1:2.2, the reaction is conducted at a temperature of about 15° to about 25° C., and at a pH of about 7.5 to about 10.5, and the organic solution of the 6,6'-di-O-tosyl sucrose reactant is added to the sugar alcohol solution over a period of about 15 to about 45 minutes.
 18. A cyclic sugar alcohol-sucrose produced by the process of claim 16 which is 6,6'-D-glucitol sucrose.
 19. A linear sugar alcohol-sucrose produced by the process of claim 17 which is 6,6'-di-O-D-glucitol sucrose.
 20. A product produced by the process of claim
 8. 21. A process for the preparation of a series of pentitol and alditol sugar alcohol reaction products which comprises slowly adding a substantially water-immiscible organic solvent containing a sulfonyl reactant to an alkaline, aqueous solution of a sugar alcohol, wherein a reaction takes place at the interface of the aqueous solution and the organic solution, and maintaining the reaction until a sulfonyl sugar alcohol reaction product is produced.
 22. The process of claim 21, wherein the sulfonyl reactant is selected from the group consisting of tosyl chloride, mesyl chloride, trifyl chloride, trimsyl chloride, tripsyl chloride, or 1,1'-sulfonyl diimidazole.
 23. The process of claim 21, wherein reaction conditions are controlled so that the tosyl reactant selectively reacts with the sugar alcohol at one or both of the primary hydroxyl groups in the sugar alcohol molecule.
 24. The process of claim 21, wherein the organic solvent solution containing the tosyl reactant is added to the aqueous sugar alcohol solution in a dropwise manner.
 25. The process of claim 21, wherein the organic solvent is a chlorinated organic solvent or an aromatic solvent.
 26. The process of claim 25, wherein the organic solvent is selected from the group consisting of methylene chloride, chloroform, carbon tetrachloride benzene, toluene, or a xylene.
 27. The process of claim 21, wherein the sugar alcohol is present in the alkaline aqueous solution in a concentration of about 5% by weight up to the limit of solubility of the sugar alcohol in water.
 28. The process of claim 21, wherein the concentration of the tosyl reactant in the water-immiscible organic solvent is from about 5% by weight up to the limit of solubility of the tosyl reactant in the solvent.
 29. The process of claim 21, wherein the molar ratio of tosyl reactant in the organic phase to sugar alcohol in the aqueous solution is from about 1:1 to about 4:1.
 30. The process of claim 21, wherein the reaction is conducted at a temperature in a range of about 0° to about 80° C.
 31. The process according to claim 30, wherein the molar ratio of tosyl reactant to sugar alcohol is about 2:1 to about 4:1, the reaction is conducted at a temperature of about 15° to about 25° C., and at a pH of about 7.5 to about 10.5, and the organic solution of tosyl reactant is added to the sugar alcohol solution over a period of about 15 to about 45 minutes.
 32. The process of claim 21, wherein the sulfonyl reactant is a tosyl chloride in a substantially water-immiscible organic solvent.
 33. A product produced by the process of claim
 21. 34. Sugar alcohols linked through either of their primary hydroxyl positions to one or more primary hydroxyl groups of sucrose, sugar alcohols, oligosaccharides, or polysaccharides and their lower molecular weight analogs.
 35. The sugar alcohol according to claim 34 which is linked through either of its primary hydroxyl positions to either primary hydroxyl group of sugar alcohols selected from the classes consisting of the alditols and the pentitols.
 36. The sugar alcohol, selected from the classes consisting of the alditols and pentitols, according to claim 34 which is linked through either of its primary hydroxyl groups to the 6- or 6' positions of sucrose.
 37. The sugar alcohol, selected from the classes consisting of the aiditols and pentitols, according to claim 34 which is linked through either of its primary hydroxyl groups to one or more primary hydroxyl position of cyclodextrins.
 38. The sugar alcohol, selected from the classes consisting of the alditols and pentitols, according to claim 34 which is linked through either of its primary hydroxyl groups to multiple primary hydroxyl position of polysaccharides selected from the group consisting of cellulose, amylose, amylopectin, chitosan and pullulan or their lower molecular weight analogs.
 39. A process for the preparation of a poly-6-O-substituted-polysaccharide product which comprise slowly adding a sulfonyl halide dissolved in a substantially water-immiscible organic solvent to a polysaccharide dissolved in an aqueous alkaline solvent, wherein a reaction takes place at the interface of the aqueous solution and the organic solution, and maintaining favorable reaction conditions until the desired poly-6-O-sulfonyl-polysaccharide product is formed and recovered.
 40. The process of claim 39, wherein the sulfonyl reactant is selected from the group consisting of tosyl chloride, mesyl chloride, trifyl chloride, trimsyl chloride, tripsyl chloride, or 1,1'-sulfonyl diimidazole.
 41. The process of claim 39, wherein the sulfonyl reactant is a tosyl chloride in a substantially water-immiscible organic solvent.
 42. The process according to claim 39, wherein the polysaccharide is selected from the group consisting of cellulose, amylose, amylopectin, pullulan and chitosan, or their lower molecular weight analogs.
 43. The process according to claim 39, wherein the tosyl halide is dissolved in toluene, the polysaccharide is dissolved in dilute aqueous alkali hydroxide, the alkaline aqueous solution exhibits a pH of about 7.5 to about 10.5, the temperature is in the range of about 15° to about 25° C., and the product is recovered by centrifugation of the aqueous phase and dissolution in pyridine.
 44. The process according to claim 39, wherein the tosylated polysaccharide is dissolved in dry pyridine and dry chloroform, the initial reaction temperature is below about -50° C. and which is eventually raised to a temperature in the range of about 15° C. to about 25° C. to complete the reaction.
 45. The process according to claim 39, wherein the polysaccharide is alpha-cellulose, which is initially dissolved in an aqueous solution of 5% cadmium oxide in 28% ethylenediamine.
 46. A process for the preparation of a poly-6-O-sucro polysaccharide which comprises adding an aqueous alkaline solution of sucrose to a poly-6-O-tosyl polysaccharide solution prepared according to the process of claim 39, and maintaining the reaction conditions until the poly-6-O-sucro polysaccharide is formed and recovered.
 47. The process according to claim 46, wherein the polysaccharide is selected from the group consisting of cellulose, amylose, amylopectin, pullulan and chitosan, or their lower molecular weight analogs.
 48. A process for the preparation of a poly-6-O-sugar alcohol polysaccharide which comprises adding an aqueous alkaline solution of a sugar alcohol to a poly-6-O-tosyl polysaccharide solution prepared according to the process of claim 39, and maintaining the reaction conditions until the poly-6-O-sugar alcohol polysaccharide is formed and recovered.
 49. The process according to claim 48, wherein the polysaccharide is selected from the group consisting of cellulose, amylose, amylopectin, pullulan and chitosan, or their lower molecular weight analogs.
 50. The process according to claim 49, wherein the sugar alcohol is selected from the groups consisting of the alditols and the pentitols.
 51. A product produced by the process of claim
 45. 52. A product produced by the process of claim
 46. 53. A product produced by the process of claim
 47. 54. A product produced by the process of claim
 48. 55. A product produced by the process of claim
 49. 